Synthesis of steroids



United tates Patent SYNTHESIS OF STEROIDS Patrick A. Diassi, Westfield, and Josef Fried, New Bruns- 4 Claims. (Cl. 260-397.3)

This invention relates to the synthesis of valuable steroids; and has for its object the provision of (I) an advantageous process of preparing the physiologically active steroid, l2ot-bromo-l1-ketoprogesterone, and of (II) 4,8,12ot-dibromopregnane-3,l1,20-trione, an intermediate useful in the preparation of said active steroid.

The process of this invention essentially comprises treating 12a-bromopregnane-3,11,20-trione with bromine in an acidic medium to form the new intermediate of this invention, 4B,l2a-dibromopregnane-3,11,20-trione, and reacting this intermediate with a lithium halide in an organic solvent of high dielectric constant, such as dimethylformamide, to yield 12ot-bromo-1l-ketoprogesterone.

The following examples illustrate the invention (all temperatures being in centigrade):

EXAMPLE 1.4fi, l Zu-DIBROMOPREGNANE- 3,11,20-TRIONE (a) 12a-br0m0pregnane-3J 1,20-tri0ne To a stirred solution of l2a-bromopregnane-3a-ol- 11,20-dione (339 mg.) in acetone (reagent grade) (12 ml.) a solution of chromic anhydride (91 mg.) and sulfuric acid (184- mg.) in water (3 ml.) is added dropwise. After 30 minutes the excess oxidizing reagent is reduced to the trivalent form with ethanol and the precipitated chromic sulfate is filtered and washed with acetone. The filtrate is diluted with water ml.) and the solution concentrated in vacuo. C1ystals of 12a-bromopregnane- 3,11,20-trione separate and are filtered, washed with water and dried. Yield about 271 mg, M. P. about 17 8-l80. Recrystallization from ethanol gives material melting at about 186-188";

Patented Sept. 9, 1958 Analysis.Calcd. for C H O Br (409.36): C, 61.61;

H, 7.14; Br, 19.52. Found: C, 61.21; H, 6.98; Br, 19.66.

(b) 4,8,12a-dibromopregnane-SJ1,20-tri0ne A solution of 12tx-brom0pregnane-3,l1,20-trione (199 mg.) in glacial acetic acid is treated dropwise with a solution (0.72 ml.) of bromine (112 rug/ml.) in acetic acid after priming with a few drops of 11% HBr in acetic acid. The solution is then poured into cold water (30 ml.) and the precipitate filtered and washed with water, 5% sodium bicarbonate and then water again. Recrystallization from ethanol gives pure 4,8,12a-dibromopregnane-il1,20-trione about (200 mg.) melting at about 164-165;

Analysis.-Calcd. for C H O Br (488.27): C, 51.65; H, 5.78; Br, 32.74. Found: C, 51.71; H, 5.61; Br, 34.00.

EXAMPLE 2.-120cBROMO-l l-KETO- PROGESTERONE A solution of 4B,l2a-dibromopregnane-3,11,20-trione (5.80 g.) and lithium chloride (1.90 g.) in dimethylformamide mg.) is heated on a steam bath for 3 hours. It is then concentrated in vacuo to about 40 ml. and water (15 ml.) is added to the hot solution. On cooling, crystalline needles separate which are filtered, washed with water and dried. Weight about 2.59 g., M. P. 165167; [211 +82.4 (CHCl 32 237m,u(e=15,200); my 5.85, 6.00, 6.18, The properties of the above sample are identical with that of an authentic sample of 12u-bromo-11-ketoprogesterone.

The invention may be variously otherwise embodied within the scope of the appended claims.

What is claimed is:

l. 4/3,l2cc-dibromopregnane-3,l1,20-trione.

2. A process for preparing 4,8,l2a-dibromopregnane-3, 11,20-trione, which comprises treating l2a-bromopregmane-3,11,20-trione with bromine in an acidic medium and recovering the 4B,l2a-dibromopregnane-3J1,20-tri one formed.

3. A process for preparing 12m-bromo-l1-ketoprogesterone, which comprises treating 4,8,l20t-CllbIOmO- pregnane-3,l 1,20-trione with lithium halide in an organic solvent of high dielectric instant and recovering the ibromo-l l-ketoprogesterone formed.

4. The process of claim 3 wherein the lithium halide is lithium chloride and the solvent is dimethyl formamide.

No references cited. 

1. 4B,12A-DIBROMOPREGNANE-3,11,20-TRIONE. 